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Latest Lutonix AV Clinical Results

Lutonix AV IDE Clinical Trial

Skyi PangVascular Surgeon

Hong Kong

Disclosure

Speaker name:

Skyi Yin Chun Pang

I have the following potential conflicts of interest to report:

Consulting

Employment in industry

Stockholder of a healthcare company

Owner of a healthcare company

Other(s)

I do not have any potential conflict of interest

Objective

Lutonix AV IDE Clinical Results

• Study design & published 6-month data

• Sub-group analysis

• 2-year outcome

• Safety and mortality data

• Current investigations

• Practical applications in 2019

Trial DesignLutonix AV IDE Clinical Trial

ObjectiveTo assess the safety and effectiveness of the LUTONIX® 035 AV Drug Coated Balloon PTA Catheter in the treatment of dysfunctional AV fistulae

Number of Patients/Sites

285 randomized subjects at 23 clinical sites

Primary Effectiveness Endpoint

Target Lesion Primary Patency (TLPP) - 6 months

Primary Safety EndpointFreedom from any serious adverse event(s) involving the AV access circuit through 30 days

Follow Up 1, 3, 6, 9, 12, 18, 24 month visits

StatusFirst Subject: June 2015Enrollment Completion: March 2016

✓ Prospective✓ Multi-Center✓ Randomized (1:1)

✓ Core Lab Adjudicated✓ Clinical Events Committee (CEC)✓ Data & Safety Monitoring Board (DSMB)

Lutonix AV IDE Clinical TrialClinical Trial Sites

Investigator Site Name State Investigator Site Name State

Balamuthusamy,

SaravananTarrant Vascular Clinic TX Nadolski, Greg Hospital of the University of PA PA

Waheed, Umar Southwest Vascular Ctr AZ Atray, Naveen Capital Nephrology Medical CA

Lipkowitz, GeorgeRenal &Transplant Assoc of

NEMA Bratton, Charles Medical University of SC SC

Saad, Theodore Nephrology Associates DE Pflederer, Timothy Renal Care Associates, S.C. IL

Hoggard, Jeffrey Capital Nephrology Assoc. NC Kamel, AhmedUniversity of Alabama at

Birmingham (UAB)AL

Peeler, David University Vascular Access TN Schultz, Scott Minnesota Vascular Surgery Ctr MN

Neyra, RoxanaArizona Kidney Disease and

Hypertension CenterAZ Wilkins, Luke University of Virginia VA

Lawless, Mike Life Access Center OK Irani, Zubin Massachusetts General Hospital MA

Licht, Jonah Providence Interventional RI Tasse, Jordan Rush University IL

Makris, Angelo Chicago Access Care IL Davanzo, William Phoebe Putney Memorial Hospital GA

Molnar, RobertSan Antonio Kidney

DiseaseCtrTX Resnick, Scott Northwestern IL

Kramer, Ari Michigan Vascular Access MI Ross, John Access Connections SC

Chan, Micah Spartanburg Regional Hpt SC

Lutonix AV IDE Clinical TrialDevice Description

• 2 µg/mm2 paclitaxel + polysorbate and sorbitol excipients

• 4-12 mm diameters, 40-100 mm lengths

• .035” guidewire compatible, nylon, semi-compliant balloon

• Over the wire, co-axial shaft

• Nominal 6atm, RBP up to 12atm

Study Device: LUTONIX® 035 DCB

Photo courtesy of BD

Primary Endpoint – 6 Month ResultsLutonix AV IDE Clinical Trial

Trerotola et al, Clin JASN 13:1215-1224, 2018

Sachdeva B, Abreo K, Clin JASN 13:1140-1141, 2018

“The preliminary findings of this study are encouraging and hopefully, will be borne out over the 12 and 24 months of observation. It is our hope that DCB angioplasty will delay recurrent stenosis in AVFs and thereby, decrease morbidity and cost for patients on hemodialysis.”

Re-interventions

LTX DCB(n=141)

StandardPTA

(n=144)

P DCB vs. Control

Number of interventions,

180 days44 64 0.034 31.3% Fewer

Number of interventions,

210 days58 85 0.012 32.8% Fewer

Lutonix AV IDE Clinical TrialSubgroup Analyses

• Antiplatelet agents

• Fistula age

• Diabetes

• Previous intervention

• Fistula location

• Target lesion location

Lutonix AV IDE Clinical TrialAntiplatelet: Aspirin or Clopidogrel

Post-Index Procedure6 Mo. TLPP Diff. P-val

Antiplatelet? LTX Control (95% CI)n/s

Yes-6 months

47/67 (70.1%) 36/63 (57.1%)13.0%

(-3.4%, 29.4%)

No 42/59 (71.2%) 52/77 (67.5%)3.7%

(-11.9%, 19.2%)

Yes-12 months

23/61 (37.7%) 15/62 (24.2%)13.5%

(-2.7%, 29.7%)

No 23/53 (43.4%) 30/70 (42.9%)0.5%

(-17.1%, 18.2%)

Yes-24 months

13/64 (20.3%) 12/64 (18.8%)1.6%

(-12.2%, 15.3%)

No 9/42 (21.4%) 13/61 (21.3%)0.1%

(-16.0%, 16.2%)

• “Antiplatelet treatment protects fistula from thrombosis or loss of patency…..” • Palmer et al, Antiplatelet therapy to prevent hemodialysis vascular access failure: Systematic review and meta-

analysis. Am J Kidney Dis 2013; 61(1):112-122

• “... the use of antiplatelet agents prevented the loss of VA patency in a dose–response manner”• Hsu et al. Antiplatelet agents maintain arteriovenous fistula and graft function in patients receiving

hemodialysis: A nationwide case-control study. PLoS one 2018; 13

Lutonix AV Clinical TrialAge of Fistula

6 Mo. TLPP Diff. 12 Mo. TLPP Diff. 24 Mo. TLPP Diff.P-val

Age of Fistula

LTX Control (95% CI) LTX Control (95% CI) LTX Control (95% CI) n/s

<= 6 Months 2/3 (66.7%)

3/4 (75.0%)

-8.3% (-76.5%, 59.8%)

1/3 (33.3%)

3/4 (75.0%)

-41.7% (-100.0%, 26.5%)

0/2 (0%)

2/3 (66.7%)

66.7% (13.3%, 100.0%)

6-12 Months 10/14 (71.4%)

14/26 (53.8%)

17.6%(-12.9%, 48.0%)

8/12 (66.7%)

7/24 (29.2%)

37.5% (5.2%, 69.8%)

4/11 (36.4%)

5/24 (20.8%)

15.5%(-17.2%, 48.3%)

> 12 Months 77/109 (70.6%)

71/110 (64.5%)

6.1%(-6.3%, 18.5%)

37/99 (37.4%)

35/104 (33.7%)

3.7% (-9.4%, 16.9%)

18/93 (19.4%)

18/98 (18.4%)

1.0%(-10.1%, 12.1%)

• “…the newer the AVF is at angioplasty, the shorter the post-intervention primary patency duration. Angioplasty in AVFs less than 6 months of age….significantly increased the risk of postinterventionprimary patency loss.” • Neuen et al, Factors associated with patency following angioplasty of hemodialysis fistulae JVIR

2014;25:1419-1426

• “…the older the AVF, the smaller the probability of recurrence”• Heye et al, Factors influencing technical success and outcome of percutaneous balloon angioplasty in de novo

native hemodialysis arteriovenous fistulas Eur J Rad 2012;81;2298-2303

Lutonix AV IDE Clinical TrialDiabetes



Yes49/73

(67.1%)

57/91 (62.6%)

4.5% (10.2%,19.1%)

26/67 (38.8%)

30/88 (34.1%)

4.7%

(-10.6%, 20.0%)

14/63 (22.2%)

15/82 (18.3%)

3.9%

(-9.3%, 17.2%)

No40/53

(75.5%)

31/49 (63.3%)

12.2%

(-5.6%, 30.0%)

20/47 (42.6%)

15/44 (34.1%)

8.5%

(-11.4%, 28.4%)

8/43 (18.6%)

10/43 (23.3%)

-4.7%

(-21.8%, 12.5%)

• “The presence of diabetes mellitus predicted restenosis of AV fistulas after PTA…”– Wu et. al, Baseline plasma glycemic profiles but not inflammatory biomarkers predict symptomatic

restenosis after angioplasty of arteriovenous fistulas in patients with hemodialysis, Atherosclerosis 2010;209:598-600

• “Patients with diabetes mellitus have higher risk for early dysfunction”– Heye et al, Factors influencing technical success and outcome of percutaneous balloon angioplasty in

de novo native hemodialysis arteriovenous fistulas European Journal of Radiology 2012;81:2298-2303

• “Early dysfunction was positively correlated with diabetes”– Atkas et al, Percutaneous transluminal balloon angioplasty in stenosis of native hemodialysis

arteriovenous fistulas: technical success and analysis of factors affecting post procedural fistula patency Diagn Interv Radiol 2015;21:160-166

Lutonix AV IDE Clinical TrialPrevious Intervention



Yes 75/109 (68.8%)

72/121 (59.5%)

9.3%(-3.0%, 21.6%)

38/99 (38.4%)

35/115 (30.4%)

7.9% (-4.8%, 20.7%)

17/92 (18.5%)

18/109 (16.5%)

2.0%(-8.6%, 12.5%)

No14/17

(82.4%)

16/19 (84.2%)

-1.9% (-26.3%, 22.6%)

8/15 (53.3%)

10/17 (58.8%)

-5.5% (-39.9%, 28.9%)

5/14 (35.7%)

7/16 (43.8%)

-8.0% (-43.0%, 26.9%)

• “…the only predictor of secondary patency was a previously failed and abandoned AVF”– Neuen et al, Factors associated with patency following angioplasty of hemodialysis fistulae JVIR

2014;25:1419-1426

• “…early dysfunction was significantly higher…in failed vascular access groups after initial PTA…” – Kim et al, Factors affecting patency following successful percutaneous intervention for dysfunctional

hemodialysis vascular access Ann Vasc Surg 2018;47:54-61

Lutonix AV IDE Clinical TrialPrevious Intervention by Time


PreviousIntervention


> 90 days59/82

(72.0%)

65/101 (64.4%)

7.60% (-5.9%, 21.1%)

29/73 (39.7%)

33/96 (34.4%)

5.4%(-9.4%, 20.1%)

13/67 (19.4%)

17/90 (18.9%)

0.5%(-11.9%, 13.0%)

< = 90 days 16/27 (59.3%)

7/20 (35.0%)

24.30% (-3.7%, 52.2%)

9/26 (34.6%)

2/19 (10.5%)

24.1% (1.2%, 47.0%)

4/25

(16.0%)

1/19

(5.3%)

10.7%(-6.8%, 28.3%)

No previous intervention

14/17 (82.4%)

16/19 (84.2%)

-1.90% (-26.3%, 22.6%)

8/15 (53.3%)

10/17 (58.8%)

-5.5%(-39.9%, 28.9%)

5/14

(35.7%)

7/16

(43.8%)

-8.0%(-43.0%, 26.9%)

• “…early occurrence was associated with a lower secondary patency rate”– Atkas et al, Percutaneous transluminal balloon angioplasty in stenosis of native hemodialysis

arteriovenous fistulas: technical success and analysis of factors affecting post procedural fistula patency Diagn Interv Radiol 2015; 21:160-166

Lutonix AV IDE Clinical TrialFistula Location


Location LTX Control (95% CI) LTX Control (95% CI) LTX Control (95% CI) n/s

AcrossAntecubital

Fossa

4/6

(66.7%)

5/7 (71.4%)

-4.8%

(-55.2%, 45.7%)

1/6

(16.7%)

3/6

(50.0%)

-33.3%

(-83.2%, 16.6%)

1/6

(16.7%)

2/5

(40.0%)

-23.3%

(-75.6%, 28.9%)

Forearm30/41

(73.2%)

22/31 (71.0%)

2.2%

(-18.8%, 23.2%)

16/36

(44.4%)

11/29 (37.9%)

6.5%

(-17.5%, 30.5%)

7/34

(20.6%)

6/26

(23.1%)

-2.5%

(-23.6%, 18.7%)

Upper Arm55/79

(69.6%)

60/101 (59.4%)

10.2%

(-3.7%, 24.2%)

29/72

(40.3%)

31/96 (32.3%)

8.0%

(-6.7%, 22.7%)

14/66 (21.2%)

17/93

(18.3%)

2.9%

(-9.7%, 15.5%)

• “Upper arm fistulae were associated with reduced postinterventionprimary patency”• Neuen et al, Factors associated with patency following angioplasty of hemodialysis fistulae JVIR

2014;25:1419-1426

• Upper-arm AVFs predicted shorter primary patency after angioplasty compared with forearm AVF• Rajan et al, Dysfunctional autogenous hemodialysis fistulas: Outcomes after angioplasty- Are there

clinical predictors of patency? Radiology 2004;232:508-515

Lutonix AV IDE Clinical TrialTarget Lesion Location

Lutonix AV IDE Clinical TrialTarget Lesion Location


Target Lesion

LocationLTX Control (95% CI) LTX Control (95% CI) LTX Control (95% CI) n/s

Anastomotic13/17

(76.5%)

8/14 (57.1%)

19.3%

(-13.5%, 52.2%)

7/16

(43.8%)

3/13

(23.1%)

20.7%

(-12.7%, 54.1%)

3/16

(18.8%)

1/13

(7.7%)

11.1%

(-12.9%, 35.0%)

Cephalic arch13/25

(52.0%)

14/31 (45.2%)

6.8%

(-19.4%, 33.1%)

5/23

(21.7%)

9/31

(29.0%)

-7.3%

(-30.5%, 15.9%)

1/22

(4.5%)

1/29

(3.4%)

1.1%

(-9.9%, 12.0%)

In cannulation

zone8/11

(72.7%)

11/16 (68.8%)

4.0%

(-30.8%, 38.7%)

6/10

(60.0%)

7/15

(46.7%)

13.3%

(-26.2%, 52.8%)

3/9

(33.3%)

5/14

(35.7%)

-2.4%

(-42.1%, 37.3%)

Inflow13/17

(76.5%)

22/28 (78.6%)

-2.1%

(-27.4%, 23.1%)

9/16

(56.3%)

11/25 (44.0%)

12.3%

(-18.9%, 43.4%)

5/14

(35.7%)

8/23

(34.8%)

0.9%

(-30.8%, 32.7%)

Near cannulation

zone

8/11 (72.7%)

7/8 (87.5%)

-14.8%

(-49.7%, 20.1%)

3/9

(33.3%)

3/5

(60.0%)

-26.7%

(-79.5%, 26.2%)

1/8

(12.5%)

1/4

(25.0%)

-12.5%

(-60.7%, 35.7%)

Outflow25/31

(80.6%)

20/34 (58.8%)

21.8%

(0.2%, 43.4%)

11/28

(39.3%)

9/34

(26.5%)

12.8%

(-10.6%, 36.2%)

7/26

(26.9%)

6/33

(18.2%)

8.7%

(-12.8%, 30.3%)

Swing point9/14

(64.3%)

6/9 (66.7%)

-2.4%

(-42.1%, 37.3%)

5/12

(41.7%)

3/9

(33.3%)

8.3%

(-33.2%, 49.9%)

2/11

(18.2%)

3/9

(33.3%)

-15.2%

(-53.5%, 23.2%)

• Cannulation zone…..more than intimal hyperplasia?• Roy-Chaudhury et al, Hemodialysis vascular access dysfunction: A cellular and molecular viewpoint JASN

2006;17(4):1112-1127

• “Swing-segment lesions predispose to early fistula failure”• Badero et al, Frequency of swing-segment stenosis in referred dialysis patients with angiographically

documented lesions Am J Kidney Dis 2008;51(1):93-98

• Cephalic arch lesions more difficult to treat• Rajan et al, Prevalence and Treatment of Cephalic Arch Stenosis in Dysfunctional Autogenous

Hemodialysis Fistulas JVIR 2003;14:567-573

Lutonix AV IDE Clinical Trial24 Month Data


Efficacy- Interim 24 Month TLPP

*One-sided p-value

LTX DCB

(N=141)

Standard PTA

(N=144)

Difference

% (95% CI) P-value*

730 Day Event Free 0.0513

Rate (SE) 32.1% (4.5%) 24.7% (4.4%) 7.4% (6.3%)

95% CI (23.5%, 41.0%) (16.5%, 33.7%) (-5.0%, 19.8%)

Data shown are interim, site reported and subject to change

LU/9010/0118/0058c

Lutonix AV IDE Clinical TrialMortality at 24 Months

DescriptionLutonix (n=141)

Control (n=144)

P Value

Number of Deaths at 24

Months33 (23.4%) 26 (18.1%) P=0.265

N= 4 voluntarily withdrew from dialysis- LutonixN= 1 voluntarily withdrew from dialysis- Control

U.S. 2 year mortality on hemodialysis- 33.2%1

1. USRDS 2018 Chapter 5 Mortality, Table 5.3

Lutonix AV Clinical TrialLutonix AV Clinical Program

TitleNumber of Subjects

Lutonix AV Clinical Trial - Complete N=285

Lutonix AV Real World Global Registry - Enrolled N=324

Lutonix AV Post Approval Study – Enrolling N=213

Total N=822

Lutonix AV Global Registry6 Month Data

Lutonix AV Global Registry

73.5% TLPP at 6 Months

6 Month TLPP ResultsLutonix AV IDE Clinical Trial

71.4% TLPP at 6 Months

Real World treated lesions; Central vein, ISR, AVG/AVF, Cephalic Arch, Restenotic, etc.

TLPP ends with a clinically driven re-intervention of the target lesion or access thrombosis. Kaplan Meier modified intent to treat.

Mature, dysfunctional fistulae. Central vein and ISR excluded. Restenotic and previous thrombosis included.

Lutonix AV IDE Clinical TrialSummary

DCB effect was not statistically different between subgroups

•DCB appears to work equivalently across access history/lesion location

Mortality rate was comparable to control arm

•None of the deaths were related to the test device or the procedure

Additional analyses to follow

•> 800 subjects part of a Lutonix AV protocol

Thank You

Latest Lutonix AV Clinical Results


Skyi PangVascular Surgeon

Hong Kong

lutonix av ide clinical trial - lincapac2019.cncptdlx.com · licht, jonah providence interventional...

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